Team:EPF-Lausanne/Project Abstract

From 2009.igem.org

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The most important assets of our project are the different control mechanisms. Since these are very much dependent on kinetic and other constants, Dr. Coli heavily relies on proper <a href="https://2008.igem.org/Team:KULeuven/Model/Overview">modeling</a>. Our Dry-Lab team has spent its summer setting up a computational model of Dr. Coli to completely simulate his actions. We constructed models of all the subsystems (components) in both CellDesigner and Matlab. All these subsystems have been characterised by their ODE's and have been simulated thoroughly. Together they form our <a href="https://2008.igem.org/Team:KULeuven/Model/FullModel">full model</a> of Dr. Coli. These models are only capable of simulating the behaviour of one Dr. Coli cell, so we implemented our own Software Tool that can work with <a href="https://2008.igem.org/Team:KULeuven/Model/MultiCell">multi cellular models</a>.
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<img src="https://static.igem.org/mediawiki/2008/8/86/5652strip.gif" border="0" alt="Parameters are everything" />
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After building the model frame, it was time to add the physical relevance to it. Kinetic constants were searched for and investigated by means of previous iGEM teams (e.g. <a href="http://parts.mit.edu/igem07/index.php?title=ETHZ/Parameters">ETHZ 2007</a>), the parts characterizations on the Registry of Standard Biological Parts and popular biological literature databases such as <a href="http://www.hubmed.org">Hubmed</a>, ...
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Our own contribution would revolve around <a href="https://2008.igem.org/Team:KULeuven/Data/Overview">data analysis</a> of the produced parts.
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<img src="https://static.igem.org/mediawiki/2008/f/f8/10797strip.gif" border="0" alt="Dilbert.com" />
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Working with concepts as modularity and abstraction, we worked out every subsystem (Output, Memory, Filter, ...) to eventually merge them all in our <a href="https://2008.igem.org/Team:KULeuven/Model/FullModel">full model</a>. By trial and error the system was adapted to achieve desired output quantities (amount of molecules, proteins, ...) given a representative input.
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To take it a step further, a <a href="https://2008.igem.org/Team:KULeuven/Model/MultiCell">multi-cell model</a> was build, to analyse crucial steps in cell division (e.g. Memory inheritance).
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A <a href="https://2008.igem.org/Team:KULeuven/Model/Diffusion">diffusion model</a> was made to investigate HSL diffusion towards neighbouring cells and see what effects this generated on their <a href="https://2008.igem.org/Team:KULeuven/Project/Inverter">Invertimer</a> system.
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<h3>Interesting Links</h3>
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<li>[http://www.nature.com/nature/comics/syntheticbiologycomic/index.html Synthetic Biology comic]</li>
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<li>[http://partsregistry.org/Main_Page Registry of Standard Biological Parts]</li>
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<li>[http://www.kuleuven.be/bioscenter BioSCENTer]</li>
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<ul class="general-links">
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<li>[[Team:KULeuven/Software/MultiCell|KUL MultiCell Toolbox]]</li>
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<li>[[Team:KULeuven/Software/Simbiology2LaTeX|KUL Simbiology2LaTeX Toolbox]]</li>
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<li>[[Team:KULeuven/Tools/Navigation_Bar|KUL Dropdown (utility)]]</li>
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<a href="https://static.igem.org/mediawiki/2008/5/50/Microbe-kombat.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/a/aa/Microbe-kombat.png">Microbe Kombat</a>
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<a href="https://static.igem.org/mediawiki/2008/8/81/Bacteria.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/1/10/Bacteria_Cannibals.png">Bacteria Cannibals</a>
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<a href="https://static.igem.org/mediawiki/2008/4/46/Dna-double_helix.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/1/1b/Helix-intro.png">Double Helix</a>
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<a href="https://static.igem.org/mediawiki/2008/f/f6/Bacteria_pairs.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/e/e5/Bacteria_pairs.PNG">Bacteria Pairs</a>
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<a href="https://static.igem.org/mediawiki/2008/8/85/Bacteria_solitaire.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/d/d9/Bacteria_solitaire.PNG">Bacteria Solitaire</a>
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<a href="https://static.igem.org/mediawiki/2008/1/12/MathAttack.swf" onClick="return popup(this,'notes')"><img src="https://static.igem.org/mediawiki/2008/e/e7/Math_Attack.png">Math Attack</a>
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<li><a href="http://www.youtube.com/watch?v=x5yPkxCLads" target="blank">PCR song</a></li>
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<h3>Notebook ({{CURRENTMONTHNAME}})</h3>
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<h3>Visitors &nbsp; &nbsp; &nbsp; &nbsp; <a id="geo" target="blank" href="http://www.searchandgo.com/geo/"><img src="http://www.searchandgo.com/geo/factory.php" rel="nofollow" alt="Visitor locations"></a></h3>
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<li><strong>Amount:</strong> &nbsp; <a><img src="http://www.yourhitstats.com/Buy_Links-3717204.png" rel="nofollow" alt="Amount of visitors"></a></li>
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<li><a target="blank" href="http://www4.clustrmaps.com/counter/maps.php?url=https://2008.igem.org/Team:KULeuven" rel="nofollow" id="clustrMapsLink"><img src="http://www4.clustrmaps.com/counter/index2.php?url=https://2008.igem.org/Team:KULeuven" style="border:0px;" alt="Locations of visitors to this page" title="Locations of visitors to this page" id="clustrMapsImg" onerror="this.onerror=null; this.src='http://www2.clustrmaps.com/images/clustrmaps-back-soon.jpg'; document.getElementById('clustrMapsLink').href='http://www2.clustrmaps.com';" /></a></li>
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Revision as of 07:48, 2 September 2009

Contents


Project Abstract





#kul div {text-align: justify;}

Our wiki has been frozen. For future updates we advise you to redirect to iGEM's Main Page. To follow our adventure at the Jamboree in Boston, keep an eye on our online BLOG.


Welcome to the KULeuven IGEM 2008 Homepage!

Enjoy the hard work we delivered, feel free to contact us at igem@kuleuven.be and visit our university/sponsor (BioSCENTer) iGEM page!

Synthetic Biology: BioSCENTer and iGEM

Synthetic biology is a new challenge in biosciences. It combines biology and engineering principles to design and build new biological functions and systems. Examples are abound: cancer cell invading bacteria, microbes that take pictures, antimalarial drug producers,... The advantage of using living systems for these purposes is that, once they are designed and built, they are self-reproducible. The challenge, however, lies exactly within the design and construction: making biological circuits and devices as robust and predictive as their electrical counterparts. ...

The Team

The KULeuven team consists of 12 enthusiastic students selected out of three faculties, 4 civil engineers, 4 bio-engineers and 4 biochemists. More information on the team members can be found on the Students page or by scrolling over the heads of the students.

Maarten Breckpot
Maarten Breckpot

Studies:
1st Master of Applied Sciences and Engineering – Mathematical Engineering
Country:
Belgium
Nick Van Damme
Nick Van Damme

Studies:
1st Master of Applied Sciences and Engineering – Mathematical Engineering
Country:
Belgium
Benjamien Moeyaert
Benjamien Moeyaert

Studies:
3rd Bachelor of Biochemistry and Biotechnology
Country:
Belgium
Stefanie Roberfroid
Stefanie Roberfroid

Studies:
3rd Bachelor of Bioscience Engineering – Biomolecular Engineering
Country:
Belgium
Dries Vercruysse
Dries Vercruysse

Studies:
1st Master of Applied Sciences and Engineering - Nanoscience and Nanotechnology
Country:
Belgium
Andim Doldurucu
Andim Doldurucu

Studies:
1st Master of Bioscience Engineering – Nanoscience and Nanotechnology
Country:
Turkey
Hanne Tytgat
Hanne Tytgat

Studies:
3rd Bachelor of Biochemistry and Biotechnology
Country:
Belgium
Elke Van Assche
Elke Van Assche

Studies:
3rd Bachelor of Bioscience Engineering – Biomolecular Engineering
Country:
Belgium
Jan Mertens
Jan Mertens

Studies:
1st Master of Bioscience Engineering – Biomolecular Engineering
Country:
Belgium
Nathalie Busschaert
Nathalie Busschaert

Studies:
3rd Bachelor of Chemistry
Country:
Belgium
Jonas Demeulemeester
Jonas Demeulemeester

Studies:
1st Master of Biochemistry and Biotechnology
Country:
Belgium
Antoine Vandermeersch
Antoine Vandermeersch

Studies:
2nd and 3rd Bachelor of Applied Sciences and Engineering – Electrical and Materials Engineering
Country:
Belgium

The Project

Our team’s project is Dr. Coli, an E. coli bacterium that produces a drug when and where it is needed in the human body. It does this in an intelligent way, such that the drug production meets the individual patient’s needs. And when the patient is cured, Dr. Coli eliminates itself from the body. To achieve this goal we divided our project into several subsystems. A detailed description about every subsystem can be found by clicking on one of the following pictograms.




scroll over the pictograms to get a short description or click on them to go to the corresponding page

Modeling

The most important assets of our project are the different control mechanisms. Since these are very much dependent on kinetic and other constants, Dr. Coli heavily relies on proper modeling. Our Dry-Lab team has spent its summer setting up a computational model of Dr. Coli to completely simulate his actions. We constructed models of all the subsystems (components) in both CellDesigner and Matlab. All these subsystems have been characterised by their ODE's and have been simulated thoroughly. Together they form our full model of Dr. Coli. These models are only capable of simulating the behaviour of one Dr. Coli cell, so we implemented our own Software Tool that can work with multi cellular models.

Parameters are everything

After building the model frame, it was time to add the physical relevance to it. Kinetic constants were searched for and investigated by means of previous iGEM teams (e.g. ETHZ 2007), the parts characterizations on the Registry of Standard Biological Parts and popular biological literature databases such as Hubmed, ... Our own contribution would revolve around data analysis of the produced parts.

Dilbert.com

Working with concepts as modularity and abstraction, we worked out every subsystem (Output, Memory, Filter, ...) to eventually merge them all in our full model. By trial and error the system was adapted to achieve desired output quantities (amount of molecules, proteins, ...) given a representative input.

To take it a step further, a multi-cell model was build, to analyse crucial steps in cell division (e.g. Memory inheritance). A diffusion model was made to investigate HSL diffusion towards neighbouring cells and see what effects this generated on their Invertimer system.


Visitors         Visitor locations

  • Amount:   Amount of visitors
  • Locations of visitors to this page




What we want to do

Light-sensitive proteins can easily be found in nature, but they have never been cloned into other cells. In this project, our aim is to design a fusion protein that would allow genetic regulation through light control.

Therefore we are working on cloning strategies that would allow us to fuse a light-sensitive domain (LovTAP in our case) with a regulatory domain (like the Trp operon). The idea is to allow transmission of the conformational change induced by light (on the light-sensitive domain) to the DNA-binding domain. This transmitted conformational change would then result in an increase or decrease of the regulatory domain's affinity for the DNA promoter site.

The overal effect would thus be a genetic expression controlled by light! There would be many applications to such a "switch" : it could kill bacteria at a certain point, stop their growth, or make them express specific proteins...

To improve the change induced by light (which is generally very unstable), we also plan a modeling part where the aim is to find which residue we would have to mutate in order to have a stable protein after the switch.

The advantage of such a system is that we could apply the light on a system and then remove it (not like if we added some liquid on the cells).


Project Abstract

Recent discoveries of photoreceptors in many organisms gave us insights into a possible interest of using light responsive genetic tools in synthetic biology. The final goal of our project is to induce a change in gene expression, more specifically to turn a gene on or off, in a living organism in response to a light stimulus.

We will use light sensitive DNA binding proteins, or light sensitive proteins that activate DNA binding proteins to transduce a light input into a chosen output, for example reporter genes like GFP, RFP. The genetic circuits allowing us to measure the activity and responsiveness of light sensitive proteins are already designed, whereas the parts and biobricks required to engineer these circuits are still in formation.

If we demonstrate that the light-induced-gene switch tool works in vivo, it would show that easier and faster tools could be used in several fields of biology. It would induce more localized, more precise (time resolution) and drastically faster genetic changes than the current used tools, which will then allow research to evolve even better.